Background: is an important fungus used in industrial applications for enzyme and acid production. To enable rational metabolic engineering of the species, available information can be collected and integrated in a genome-scale model to devise strategies for improving its performance as a host organism.
Results: In this paper, we update an existing model of metabolism to include the information collected from 876 publications, thereby expanding the coverage of the model by 940 reactions, 777 metabolites and 454 genes. In the presented consensus genome-scale model of iJB1325 , we integrated experimental data from publications and patents, as well as our own experiments, into a consistent network. This information has been included in a standardized way, allowing for automated testing and continuous improvements in the future. This repository of experimental data allowed the definition of 471 individual test cases, of which the model complies with 373 of them. We further re-analyzed existing transcriptomics and quantitative physiology data to gain new insights on metabolism. Additionally, the model contains 3482 checks on the model structure, thereby representing the best validated genome-scale model on developed until now. Strain-specific model versions for strains ATCC 1015 and CBS 513.88 have been created containing all data used for model building, thereby allowing users to adopt the models and check the updated version against the experimental data. The resulting model is compliant with the SBML standard and therefore enables users to easily simulate it using their preferred software solution.
Conclusion: Experimental data on most organisms are scattered across hundreds of publications and several repositories.To allow for a systems level understanding of metabolism, the data must be integrated in a consistent knowledge network. The iJB1325 model presented here integrates the available data into a highly curated genome-scale model to facilitate the simulation of flux distributions, as well as the interpretation of other genome-scale data by providing the metabolic context.
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http://dx.doi.org/10.1186/s40694-018-0060-7 | DOI Listing |
Genes (Basel)
January 2025
Department of Physics and Astronomy, College of Science, Clemson University, Clemson, SC 29634, USA.
Background/objectives: Predicting the effects of protein and DNA mutations on the binding free energy of protein-DNA complexes is crucial for understanding how DNA variants impact wild-type cellular function. As many cellular interactions involve protein-DNA binding, accurately predicting changes in binding free energy (ΔΔG) is valuable for distinguishing pathogenic mutations from benign ones.
Methods: This study describes the development and optimization of the SAMPDI-3Dv2 machine learning method, which is trained on an expanded database of experimentally measured ΔΔGs.
mSystems
January 2025
Biosystems and Bioprocess Engineering, IIM-CSIC, Vigo, Spain.
During batch fermentation, a variety of compounds are synthesized, as microorganisms undergo distinct growth phases: lag, exponential, growth-no-growth transition, stationary, and decay. A detailed understanding of the metabolic pathways involved in these phases is crucial for optimizing the production of target compounds. Dynamic flux balance analysis (dFBA) offers insight into the dynamics of metabolic pathways.
View Article and Find Full Text PDFToxicol Sci
January 2025
Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, MD, 21702, USA.
Because the liver plays a vital role in the clearance of exogenous chemical compounds, it is susceptible to chemical-induced toxicity. Animal-based testing is routinely used to assess the hepatotoxic potential of chemicals. While large-scale high-throughput sequencing data can indicate the genes affected by chemical exposures, we need system-level approaches to interpret these changes.
View Article and Find Full Text PDFNat Commun
January 2025
Institute of Marine Science and Technology, Shandong University, Qingdao, China.
Lignin, as the abundant carbon polymer, is essential for carbon cycle and biorefinery. Microorganisms interact to form communities for lignin biodegradation, yet it is a challenge to understand such complex interactions. Here, we develop a coastal lignin-degrading bacterial consortium (LD), through "top-down" enrichment.
View Article and Find Full Text PDFNPJ Syst Biol Appl
January 2025
The Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA, 94608, USA.
Genome-scale metabolic models (GSMM) are commonly used to identify gene deletion sets that result in growth coupling and pairing product formation with substrate utilization and can improve strain performance beyond levels typically accessible using traditional strain engineering approaches. However, sustainable feedstocks pose a challenge due to incomplete high-resolution metabolic data for non-canonical carbon sources required to curate GSMM and identify implementable designs. Here we address a four-gene deletion design in the Pseudomonas putida KT2440 strain for the lignin-derived non-sugar carbon source, p-coumarate (p-CA), that proved challenging to implement.
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